DESCRIPTION (Applicant?s abstract): Delivery of drugs to the lungs by aerosol (either via a metered dose inhaler, MDI, or nebulization of a solution) is fundamental therapy for a host of lung diseases. Aerosol administration to mechanically ventilated patients is most commonly done by a nurse or respiratory therapist. This approach can be highly variable, is prone to errors particularly in patients on multiple MDIs and nebulizers, has no means to monitor medication errors accurately, and occupies time of costly health care professionals. We have designed a computer-controlled prototype device that interfaces with a positive pressure ventilator. This device controls the time in the respiratory cycle when a liquid solution is nebulized and delivered to the lungs and, in preliminary studies in ventilated sheep, efficiently nebulizes the drug with minimal contamination of the environment. The aims of this Phase I proposal are: 1. Using the prototype device in mechanically ventilated sheep with normal lungs, maximize the amount of aerosol deposited in the lung by varying the timing and duration of nebulization during the breathing cycle, the ventilator tidal volume during nebulization, and the aerosol particle size. 2. Compare performance of the prototype device with conventional continuous nebulization in mechanically ventilated healthy sheep and sheep with acute lung injury. Upon successful completion of these aims, the next phase of development would be to refine the prototype to administer multiple MDIs and nebulizations to the ventilated subject in an automatic, controlled, and monitored fashion. We tentatively call the device AuContrAer.